Derivatives of isoascorbic acid



Fatentecl Got. 8, i946 DERIVATIVES OF ISOASCORBIC ACID Percy A. Wells, Abington, and Daniel Swern, Melrose Park, Pa., assignors to the United States of America, as represented by the Secretary of Agriculture No Drawing. Application May 11, 1942, Serial No. 442,557

7 Claims. (Cl. 260344.5) (Granted under the act of March 3, 1883, as

This application is made under the act of March 3, 1883, as amended by the act of April 30, 1928, and the invention herein described and claimed, if patented, may be manufactured and used by or for the Government of the United States of America for governmental purposes without the payment to us of any royalty thereon.

This invention relates to derivatives of isoascorbic acid and is directed more particularly to the isoascorbic acid esters of carboxylic acids and to methods for producing the same.

The empirical formula of isoascorbic acid is 081-1806 and the spatial configurations of the two enantiomorphic forms of isoascorbic acid are believed to be represented by the following structural formulas:

.351 OH H t H-Al-OH OHzOE d-Isoascorbic acid 00 ft... ("l-OH Lt... HO-(B-H CHzOH l-Isoascorbic acid It is well known that with the exception of the optical rotation enantiomorphs possess identical physical and chemical properties. In the present specification and claims the term isoas corbic acid is meant therefore to include both the dand the l-forin of isoascorbic acid.

- We have discovered that isoascorbic esters are formed by the interaction of isoascorbic acid with aliphatic monocarboxylic acids or with acyl halides derived from such acids.

These isoascorbyl esters are new compounds having valuable properties which render, them useful as components or as intermediates in the manufacture of various synthetic materials. For-example, some of the higher fatty esters of isoascorbic acid, such as for instance isoascorbyl laurate, myristate, palmitate, stearate and the like are fat soluble compounds having antiamended April 30, 1928;

oxidant properties, as claimed by Percy A. Wells and Roy W. Riemenschneider in their application, Serial No. 472,280, filed January 13, 1943,

absence, of suitable solvent or dispersing media such as pyridine and the like.

The monoesters of isoascorbic acid are obtained most readily by reacting isoascorbic acid with aliphatic monocarboxylic acids in the presence of concentrated sulfuric acid, as described in our copending application Serial No. 442,558, Patent 2,350,435.

According to this procedure the fatty acid and isoascorbic acid are dissolved in concentrated sulfuric acid and the reaction mixture is maintained at a suitable temperature for the length of time necessary to effect esterification. The

reaction products are then isolated from the solution by any suitable procedure, for example by dilution with water followed by solvent extraction.

In effecting the esterification by the above procedure we prefer to use -95 percent sulfuric acid. However, sulfuric acid of other concentrations may be employed provided that it is adapted for performing the dual function of an esterification catalyst and of a solvent for the components of the reaction mixture.

The esterification may be carried out at any temperature which will not cause any substantial sulfonation, or decomposition of the components of the reaction mixture. When percent sulfuric acid is used satisfactory results are obtained by operating at ordinary room temperature.

However, the reaction velocity of esterification processes is increased at higher temperatures and under certain conditions it may be advantageous to conduct the process at temperatures above room temperature.

An important feature of our invention is the fact that when esterification is effected in the presence of sulfuric acid by interaction of isoascorbic acid with aliphatic monocarboxylic acids the esters formed retain the characteristic properties of compounds containing an unsubstituted ene-diol group, that is the atomic grouping,

present in isoascorbic acid.

The presence of an unsubstituted ene-diol process of our invention may be established by known analytical methods.

Alkali tritrations of alcoholic solutions of the esters, for example, indicate the presence in the ester molecule of one titratable acidic enolic hydrogen. Furthermore, the esters can also be titrated essentially by the standard iodometric I Either course of the esterification reaction would yield isoascorbyl monoesters containing unsubstituted ene-diol groups.

The production of such esters is especially desirable in view of the fact that the oxidationreduction properties of isoascorbic acid are known to be caused by the presence of an unsubstituted ene-diol group.

It is known, for instance that d-isoascorbic acid is a valuable antioxidant for fatty substances and for aqueous-oil emulsions. (See Journal of Am. Chem. Soc. 1941, 63, 1279; U. S. Patent 2,159,986.) However, d-isoascorbic acid is relatively insoluble in anhydrous fatty and oily substances and this property limits its use as an antioxidant.

It was discovered that the antioxidant properties of compounds containing an unsubstituted ene-diol group are retained and'their usefulness enhanced if they are converted to derivatives soluble in fats and oils.

Some of the fat soluble isoascorbyl esters are especially valuable as antioxidants for edible fats.

As illustrative embodiments of a manner in which our invention may be carried out in practice the following examples are given:

Example 1 8.8 grams of d-isoascorbic acid and 8.0 grams of lauric acid are dissolved, at room temperature, in 100 cc. of 95 percent sulfuric acid, and the solution is allowed to stand at room temperature for about six hours.

The reaction mixture is then poured slowly and with vigorous agitation into about 500 grams of chopped ice. Agitation is continued until the oily phase of the drowned mixture has solidified. The mixture is then extracted with ether, the ether extract is washed with water until the washings are substantially acid free.

The ether extract is dried and evaporated to dryness.

The dry, light yellow residue thus obtained is powdered and washed by decantation with 200 to 300 cc. of petroleum ether (boiling range 35- 60 0.), thereby removing a small amount'of unreacted fatty acid present in the reaction product. The unreacted fatty acid is readily recoverable from the washings and may be used over again.

The light yellow residue insoluble in petroleum ether consists essentially of d-isoascorbyl mono- V laurate.

The yield is about 75-80 percent of the theory.

To remove all traces of moisture from the ester itis dried at about 60 C. under a high vacuum. For analytical purposes the product is purified by recrystallization from an ether-petroleum ether mixture.

The anhydrous d-isoascorbyl monolaurate has .the following properties:

Melting point C 78-79 Combined fatty acid percent 562 Equivalent weight by iodine titration 178.8 Neutralization equivalent 360.0

Example 2 A mixture of 27.5 grams of palmityl chloride and 17.6 grams of d-isoascorbic acid is heated for six hours to 75 C. while stirring. Esteriflcation occurs with copious evolution of hydrogen chlo- V a mixture of isoascorbyl palmitates.

Example 3 9.9 grams of myristyl chloride. 7.0 grams of d-isoascorbic acid and 40 cubic centimeters of pyridine are heated to C. for two hours. The

- reaction mixture is poured into 800 cc. of cold 5 percent aqueous sulfuric acid. The light yellow solid material formed is filtered off and dried. 12 grams of dry substance consisting essentially of mixed isoascorbyl myristates are obtained.

Example 4 8.8 grams of d-isoascorbic acid are esterlfled with 9.1 grams of myristic acid in 100 cc. of percent sulfuric acid by the procedure described in Example 1. The d-isoascorbyl monomyristate thus obtained has the following characteristics.

Melting point C 84-85 Combined fatty acids per cent 58.6 Equivalent weight by iodine titration 193.2 Neutralization equivalent 385.0

Ercample 5 Melting point C 88.5-89.5 Combined fatty acids per cent 61.8 Equivalent weight by iodine titration 208.1 Neutralization equivalent 413.0

Example 6 d-Isoascorbyl monostearate is prepared by the method described in Example 1, using 8.8 grams Melting point C 91.5-92.5

Combined fatty acids per cent 64.1 Equivalent weight by iodine titration..- 223.0 Neutralization equivalent 444.7

Example 7 d-Isoascorbyl monocaproate is prepared by the method described in Example 1, using 8.8 grams of d-isoascorbic acid, 4.6 grams of caproic acid and 100 cc. of 95 percent sulfuric acid.

Example 8 We claim:

1. Isoascorbyl mono-esters of aliphatic saturated monocarboxylic acids, said esters containing an unsubstituted ene-diol group.

2. Isoascorbic compounds represented by the formula wherein one of the substituents R and R represents an acyl radical of a saturated aliphatic monocarboxylic acid and the other represents a hydrogen atom.

3. Isoascorbyl monoesters of saturated aliphatic monocarboxylic acids said acids containing from 12 to 18 carbon atoms, said esters containing an unsubstituted ene-diol group.

4. Isoascorbyl mono-esters of lauric acid, said esters containing an unsubstituted ene-diol group.

5. Isoascorbyl mono-esters of palmitic acid, said esters containing an unsubstituted ene-diol group.

6. Isoascorbyl mono-esters of stearic acid, said esters containing an unsubstituted ene-diol group.

7. The method of producing isoascorbyl monoesters containing an unsubstituted ene-diol group which comprises reacting isoascorbic acid with a saturated aliphatic monocarboxylic acid in the presence of concentrated sulfuric acid.

PERCY A. WELLS. DANIEL SW'ERN. 

